Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer
This phase II trial is studying how well giving azacitidine together with entinostat works in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Azacitidine and Entinostat in Patients With Metastatic Colorectal Cancer|
- Confirmed Tumor Response [ Time Frame: At 6 month evaluation ] [ Designated as safety issue: No ]Each evaluable patient is classified as having a confirmed tumor response if they have either a complete response (CR) or partial response (PR) lasts at least 4 weeks. Tumor response is measured by using RECIST v1.1 (Response Evaluation Criteria in Solid Tumors). A CR is defined as a disappearance of all target lesions, and each target lymph node must have reduction in short axis to <1.0 cm. A PR is defined as a 30% decrease in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation, compared to pre-treatment measurements. The confirmed response rate is calculated as the number of confirmed CR+PR, divided by the total number of evaluable patients, with 95% confidence intervals estimated using the approach of Duffy and Santner.
- Time to Progression [ Time Frame: From the start of treatment to the earliest of the date documenting disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]Time to disease progression (TTP) is defined as the time from the start of treatment to the earliest of the date documenting disease progression or most recent assessment for patients having no progression. The distribution of TTP is estimated using the method of Kaplan-Meier.
|Study Start Date:||April 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (entinostat, azacitidine)
Patients receive 40 mg/m^2 azacitidine subcutaneously on days 1-5 and 8-10 and 7 mg oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Seven mg given orally on days 3 and 10 of a 28-day cycle
Other Names:Drug: azacitidine
On days 1-5 and 8-10 of a 28-day cycle, 40 mg/m^2 are given subcutaneously.
I. To determine the preliminary efficacy via Response Evaluation Criteria In Solid Tumors (RECIST) response rate of the combination of azacitidine and entinostat in patients with metastatic colorectal cancer.
I. Explore the effects of azacitidine and entinostat on time to progression in patients with metastatic colorectal cancer.
II. To assess the toxicity for combination azacitidine and entinostat therapy.
OUTLINE: This is a multicenter study.
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and tumor tissue samples are collected at baseline and periodically during courses 1-3 for DNA methylation, histone deacetylation activity, and acetylation of H3 and H4 histones analysis by polymerase chain reaction (PCR), western blot, and RT-PCR assays. Pharmacogenomic studies may also be conducted.
After completion of study therapy, patients are followed up every 3-6 months for up to 3 years.
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, California|
|University of Southern California|
|Los Angeles, California, United States, 90033-0804|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287-8936|
|United States, Michigan|
|Wayne State University|
|Detroit, Michigan, United States, 48202|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Saint Louis Park, Minnesota, United States, 55416|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Nilofer Azad||Mayo Clinic|